This Mentored Clinical Scientist Development Award, a program of research and career development, is proposed to establish a foundation for future independent research in behavioral neuroscience, with a focus on reproductive hormones and emotional regulation. The research component of the proposal is a series of studies investigating the hypothesis that estrogen restrains fear associated behaviors. Clinical data indicates that reproductive hormones fluxes have profound effects on the course of anxiety disorders and depression, but the neurobiological determinants of these clinical observations are not well understood. The specific aims of the research plan are to: 1) study the effects of estrogen on a battery of behavioral tests of anxiety; 2) examine the effects of estrogen on glucocorticoid and stress induced enhancement of fear behaviors; 3) examine the effects of estrogen on extrahypothalamic CRH and glucocorticoid receptors, a neuroendocrine system known to modulate fear and anxiety and 4) define the anatomic sites of estrogen action on fear behaviors. Fear associated neural circuits involving the amygsala, bed nucleus of the stria terminalis, and medial prefrontal cortex will be studied using local administration of estrogen and estrogen antagonists. The training portion of this proposal consists of basic neuroscience coursework and seminars as well as hands-on instruction in behavioral analysis and functional neuroanatomic techniques. Studies of the effects of estrogen on anxiety related neural systems provides an opportunity for the investigator to expand her area of expertise from clinical neuroendocrinology and clinical psychiatry to behavioral neuroscience where the effects of hormones on brain function can be studied more directly. This field of investigation is likely to improve understanding and treatment of anxiety and affective disorders, both of which are widely prevalent, chronic public health problems.